In research and development of medicaments, experimental animals have been used for a long time. On the other hand, it is sometimes difficult to find the efficacy and side effects of medicaments on the basis of data of experimental animals due to intrinsic metabolic functions specific to humans. Also, reduction of experimental animals is recently suggested from the viewpoint of an animal protection. In addition, high cost is incurred for clinical trials in humans. For these reasons, it is desired to reproduce artificial organs, in vitro, having the same function as living organs. Recently, regeneration medical techniques have been evolved, and thus construction of such a model has become possible.
An organ exhibits its functions within the living body when it is exposed to various fluids including blood. In order to construct a model of an organ, cell culturing must be performed in a flow system. Therefore, culturing methods using various reactors are proposed (JP Patent Publication (Kokai) No. 2001-190270 and U.S. Pat. No. 5,202,254).
In the living body, the fluid flows through a capillary to supply various substances to cells, and receive waste matters therefrom. On the other hand, for cells such as vascular endothelial cells which are directly exposed to the fluid (blood), the cells are stimulated by blood flow shearing. In order to establish culturing conditions which satisfy these requirements, cell culture in a microreactor is considered suitable for modeling of living system, and many studies have been conducted on this subject (Manabu Tokeshi et al. Anal. Chem., 74, 1565(2002); Shuichi Takayama et al., Proc. Natl. Acad. Sci. USA. 96, 5545 (1999); and M. J. Powers et al, Tissue Eng., 8, 499 (2002)).
In particular, when the liver is simulated as a model, culturing must be performed in the conditions which allow migration of substances between two culture mediums (corresponding to bile and blood) and the cells, while preventing a backward flow from the bile corresponding medium to the blood corresponding medium. A liver simulation model made from such a viewpoint is prepared by a method in which a flow is established from a blood-corresponding medium to a bile-corresponding medium and cells are cultured in the flow. However, the blood cannot be in direct contact with each other. In this respect, the aforementioned liver simulation model is not considered perfect.
There is a proposed method in which cells are cultured in two types of mediums with a diaphragm between them, practical in a bioreactor using a filamentous fungus for substance production (JP Patent Publication (Kokai) Nos. 7-322874 and 8-9958). However, these methods are not suitable for culturing animal cells and constructing a living-organ simulation model, since it is difficult to stimulate a blood flow and stimulate cells by blood flow shearing. Furthermore, as the feature of the cell culture device mentioned above, it is necessary to culture cells in a flow system for hours to days depending upon the purpose of culturing, and it is required to construct an equipment system enabling long and stable tests. In addition, it is also necessary to reduce the examination time by finding accelerating conditions, and to determine the counter-power of a sample by performing a compulsive test.